Dwight E Yin1, Meredith G Warshaw2, William C Miller3, Hannah Castro4, Susan A Fiscus5, Lynda M Harper4, Linda J Harrison2, Nigel J Klein6, Joanna Lewis7, Ann J Melvin8, Gareth Tudor-Williams9, Ross E McKinney10. 1. Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; Department of Epidemiology, Gillings School of Global Public Health, Division of Infectious Diseases, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City, Kansas City, Missouri; deyin@cmh.edu. 2. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; 3. Department of Epidemiology, Gillings School of Global Public Health, Division Infectious Diseases, Department of Medicine, School of Medicine, and. 4. Infections Group, Medical Research Council Clinical Trials Unit. 5. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; 6. Infectious Diseases and Microbiology Unit, Institute of Child Health, and. 7. Institute of Child Health and CoMPLEX, University College London, London, United Kingdom; 8. Division of Pediatric Infectious Disease, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington; and. 9. Section of Pediatrics, Imperial College London, London, United Kingdom. 10. Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina;
Abstract
BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.
BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.
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